Reactions Involving Free Radicals

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Reactions Involving Free Radicals
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Free radical reactions involve one electron
species, frequently generated by homolysis (shown
below). Note the use of an arrow with a half
head to designate the movement of one electron.
Weak bonds, like O-O bonds and X-X bonds undergo
such homolysis reactions relatively easily.
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Hydroxy radicals (HO.) and hydrogen radicals (H.)
are relatively unstable.
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However, radicals can be stabilized by resonance,
and shielded from reaction by steric hindrance,
sometimes resulting in long-lived radicals.
BHT, above, is sometimes added as a food
preservative, to prevent the process of auto
oxidation, that occurs in the presence of air and
light. Once it reacts with a peroxy radical
(above) it transfers a hydrogen atom to produce a
resonance-stabilized, hindered oxygen radical,
which does not react further.
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Another Stable Free Radical TEMPO (2,2,6,6-tetram
ethylpiperidine-1-oxyl)
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TEMPO is available commercially, but expensive
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TEMPO is often used catalytically, together with
stoichiometric amounts of inexpensive oxidants,
to oxidize alcohols to aldehydes and ketones.
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The mechanism of this reaction involves oxidation
of the N-O bond to an NO bond by the secondary
stoichiometric oxidant, which undergoes addition
of the alcohol, as shown below.
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TEMPO is also used to initiate controlled radical
polymerization reactions
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Geometry of Carbocation, Radical, and Carbanion
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Radical reactions can be divided into three
steps 1) Initiation 2) Propagation 3)
Termination
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Weaker bonds are more readily cleaved by homolysis
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Some bonds can be cleaved by heating
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Radical Initiators
AIBN
Link
Benzoyl Peroxide
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One common reaction of radicals is an atom
abstraction, with a hydrogen atom being one of
the most commonly abstracted atoms (note this
process does NOT involve a hydrogen radical).
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Radical Bromination
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Link
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Allylic (and benzylic) bromination with NBS
(N-Bromosuccinimide)
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NBS is regarded as a source of trace amounts of
Br2 via the mechanism shown below.
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Note that the free-radical bromination occurs at
the benzylic (and allylic) positions, through
resonance-stabilized radical species.
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Reductions utilizing tributyltin hydride as a
hydrogen atom donor
The Sn-H bond is relatively weak (82 kcal/mole),
relative to the C-H bond (99 kcal/mole) By
contrast, tin forms stronger bonds to bromine,
iodine, and sulfur than does carbon.
Sn-S 111 kcal Sn-Br 132 Kcal Sn-I 56
kcal Sn-H 82 kcal
C-S 65 kcal C-Br 68 kcal C-I 51 kcal C-H 99
kcal
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The use of TRIBUTYLtin derivatives has become
relatively common. The three butyl groups add
molecular weight to the tin and thus lower its
vapor pressure. (Tin compounds can be toxic by
inhalation.)
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While a clean, high-yielding reduction of an
alkyl halide is synthetically useful, it would be
even more useful if there existed a method for
reducing an alcohol to an alkane.
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The Barton-McCombie Deoxygenation
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Mechanism
Notice that the tin radical attacks the sulfur to
generate the highly stabilized tertiary radical.
(This is unlike the addition of nucleophiles to
the CO, which always occurred at the carbonyl
carbon, due to the polarized nature of the
carbonyl group.)
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Obviously the hydrogen atom is transferred from
tin to carbon relatively easily. Can other alkyl
groups be transferred from tin to carbon (by a
free-radical process)?
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Radical Reaction with Allyltributylstannane
One alkyl group that transfers (from tin to
carbon) well is the allyl group, as shown below.
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Mechanism of reaction of allyltributyltin with
alkyl halides
(Notice that another common reaction of free
radicals is addition to a CC.)
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The Barton Decarboxylation
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In the Case of a (non-radical) Decarboxylation
,Recall that
Decarboxylation produce CO2, and are thus
thermodynamically favorable. These reactions
proceed most readily when the COOH moiety is
attached to an electronegative atom, like oxygen
or nitrogen.
Unstabilized Carbanion is NOT formed
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However, even in the case of simple carboxylic
acid, decarboxylation may proceed readily, if the
resultant carbanion is stabilized by resonance,
or other electronegative substituent, as shown
for acetoacetic acid below.
Stabilized (enolate) carbanion is formed
The reaction probably proceeds through a cyclic
transition state as shown below.
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Carboxyl RADICALS, however, decarboxylate much
more readily than the corresponding acids and
carboxylate salts.
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An early decarboxylation utilizing this fact was
the Hunsdiecker reaction, shown below
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Mechanism of the Hunsdiecker Reaction
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Derek Barton developed a more reliable procedure
for decarboxylation which does not employ the use
of Br2.
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Mechanism of the Barton Decarboxylation
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Addition of radicals to double bonds
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Under certain conditions, addition of H-Br (but
not H-Cl or H-I) gives anti-Markovnikov
regiochemistry Why?
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Benzoyl Peroxide
Ascaridole
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Morris S. Kharasch
LINK
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Mechanistic Reason for Effect of Peroxides on the
Regiochemistry of Addition of H-Br to the alkene
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Free Radical Polymerization Link